Biomaterial Database

Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol. 1993

L Peacock, and J Gerlach

Research Institute of Biological Psychiatry, St. Hans Hospital, Roskilde, Denmark.

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.

UI	MeSH Term	Description	Entries
D008090	Lisuride	An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS).	Lysuride Hydrogen Maleate,Methylergol Carbamide,Arolac,Cuvalit,Dopergin,Dopergine,Lisuride Hydrochloride,Lisuride Maleate,Lisuride Maleate (1:1),Lisuride Maleate, (8beta)-Isomer,Lisuride Mesylate,Lisuride Phosphate (1:1),Lisuride, (8alpha)-(+-)-Isomer,Lysenyl,Lysurid,Revanil,Carbamide, Methylergol,Hydrochloride, Lisuride,Hydrogen Maleate, Lysuride,Maleate, Lisuride,Mesylate, Lisuride
D008297	Male		Males
D010880	Piperidines	A family of hexahydropyridines.
D002428	Cebus	A genus of the family CEBIDAE, subfamily CEBINAE, consisting of gracile or untufted capuchin species. Tufted capuchins belong to genus SAPAJUS. Members include C. capucinus, C. nigrivultatus, and C. albifrons. Cebus inhabits the forests of Central and South Americas.	Cebu,Gracile Capuchins,Monkey, Capuchin,Monkey, Ring-Tail,Monkey, Ringtail,Monkey, Ringtailed,Untufted Capuchins,White-Fronted Capuchin,Monkey, Ring-Tailed,Capuchin Monkey,Capuchin Monkeys,Capuchin, Gracile,Capuchin, Untufted,Capuchin, White-Fronted,Gracile Capuchin,Monkey, Ring Tail,Monkey, Ring Tailed,Ring-Tail Monkey,Ring-Tail Monkeys,Ring-Tailed Monkey,Ring-Tailed Monkeys,Ringtail Monkey,Ringtail Monkeys,Ringtailed Monkey,Ringtailed Monkeys,Untufted Capuchin,White Fronted Capuchin,White-Fronted Capuchins
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004409	Dyskinesia, Drug-Induced	Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)	Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D004421	Dystonia	An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)	Muscle Dystonia,Dystonia, Diurnal,Dystonia, Limb,Dystonia, Paroxysmal,Diurnal Dystonia,Dystonia, Muscle,Limb Dystonia,Paroxysmal Dystonia
D004873	Ergolines	A series of structurally-related alkaloids that contain the ergoline backbone structure.	Ergoline
D005260	Female		Females
D006220	Haloperidol	A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)	Haldol